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Ketamine may not reduce post-surgery pain, delirium

Ketamine is commonly prescribed to help alleviate post-surgery delirium and pain, but a new, multicenter trial suggests that the drug may be useless in treating these symptoms.

New research indicates that, contrary to popular opinion, ketamine is not effective in treating surgery-induced pain or delirium.

A team of anesthesiologists from Washington University School of Medicine in St. Louis, MO, and the University of Michigan Medical School in Ann Arbor set out to investigate the benefits of ketamine for patients who have recently undergone surgery.

It is currently believed that ketamine is useful for the prevention of post-surgery pain and delirium. For this reason, medical professionals - especially those who wish to avoid using opioid drugs such as morphine -
routinely prescribe the drug.

Opioids are known to reduce severe pain, but many patients who use them go on to develop an addiction disorder, particularly if they use them over a longer period of time.

The team was co-led by researcher Dr. George A. Mashour, Ph.D., an professor of anesthesiology at the University of Michigan Medical School, and Michael S. Avidan, first author of the study, and a professor of surgery and of anesthesiology at Washington University.

Explaining the context of their new research, Avidan says, "In recent years, there's been a big increase in the amount of ketamine given in the operating room because clinicians are trying to prevent pain after surgery without relying on opioid drugs."

Studying the effects of ketamine on post-surgery patients

Avidan and colleagues followed 672 patients aged 60 and older who had had surgery across four countries: the Canada, India, South Korea, and the United States.

During surgery, the patients either received no ketamine at all, a very low dose, or a slightly higher dose. All of the doses used in the study are the same as those routinely administered by healthcare professionals wishing to reduce postoperative pain in their patients.

Avidan and team then followed these patients for several days after the operation, during which time they enquired about and monitored their pain, assessed whether or not they had delirium, and measured the amount of opioids they needed to control their pain.

Delirium is a mental state characterized by confusion, disorientation, and difficulty remembering things or recognizing family and friends. Sometimes, patients with delirium can also experience agitation and hallucinations.

Some studies have estimated that delirium affects up to 50 percent of hospitalized elders, while Avidan's own previous research has set that percentage at 20.

"When patients become delirious after surgery, they tend to spend more time in the intensive care unit, have longer hospital stays, and have a greater chance of dying," explains Avidan. "Overall, patients who develop delirium have worse outcomes and are at higher risk for long-term cognitive decline. So it's really important to try to prevent it if we can."

Ketamine 'not effective' for reducing delirium or pain

Although some previous small-sample studies on humans, and a few studies in rodents, have suggested that ketamine might help recovery from anesthesia and reduce the odds of developing postoperative delirium, this new study offers a less optimistic view.

Mashour further explains the results, adding that the researchers were "particularly surprised by the lack of an effect on postoperative pain."

"Giving single doses of ketamine during surgery to prevent postoperative pain is increasingly common," Mashour says, "but our data challenge that practice and suggest that even after decades of use, more research is required if we hope to understand ketamine."

"We found that the current practice of giving low doses of ketamine to patients during surgery is not having the desired effect. So we need to determine whether higher doses might be more effective, or we need to find other alternatives to opioids.

There were various reasons to think this drug was providing protection to the brain around the time of surgery, and we hypothesized that ketamine would, in fact, reduce postoperative delirium and pain. Unfortunately, it didn't do either."

Prof. Michael S. Avidan

The researcher also adds that not only did ketamine not alleviate delirium and pain, but for some patients, it even caused hallucinations and nightmares.

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